Various strategies have been proposed in the art to rise an immune response in a subject, such as direct administration of an antigen, ex vivo stimulation and expansion of immune cells (such as T lymphocytes or dendritic cells, for instance), injection of genetically- or chemically-modified cancer cells, administration of inactivated viruses and gene therapy using nucleic acids encoding particular antigens or cytokines.
While these various approaches allow the generation of an immune response against certain types of antigens or pathogenic agents, there is still a need for better methods of eliciting, regulating or stimulating an immune response. In particular, there is a need for simple methods of generating efficient immune responses, such as efficient cellular and/or humoral immune responses, against a variety of antigens, such as tumor antigens, viral antigens or other antigens from pathogenic agents, most particularly, by oral administration.
Indeed, most commercial vaccines available today are delivered by injection, with problems of safety, patient acceptability and morbidity and which makes mass immunization more costly and less safe, particularly in resource-poor developing countries. Therefore, oral delivery offers a number of significant advantages over other routes of administration and notably compared with parenteral vaccines (simple administration and improved safety). In addition, unlike systemic immunisation, oral delivery can induce mucosal immune responses.
Thus, orally delivered vaccines are processed and presented by the digestive tract's immune system, often referred to as the gut-associated lymphoid tissue (GALT). The GALT is a complex system consisting of inductive sites (where antigens are encountered and responses are initiated) and effector sites (where local immune responses occur) linked by a homing system, whereby cells activated by antigen in the GALT migrate to the circulation and, subsequently, to the mucosa (Lavelle et al.; 2006). As a result, oral vaccination can induce immune responses locally in the gut and at distant mucosal sites, as well as systemic humoral and cellular immune responses. Oral vaccination typically generates a large amount of secretory IgA (sIgA), which plays a major role in mucosal defense.
Yet, even if the oral route of vaccine delivery represents the ideal means of delivering prophylactic and therapeutic vaccines, offering significant advantages over systemic delivery, the oral route is also the most difficult because of the numerous barriers posed by the gastrointestinal tract. To facilitate effective immunisation with peptide and protein vaccines, antigens must be protected, uptake enhanced and the innate immune response activated. Thus, numerous delivery systems and adjuvants have been evaluated for oral vaccine delivery, including live vectors, inert particles and bacterial toxins. However, developments in oral vaccines have been until now disappointing since no efficient oral immunisation has been obtained by using proteins or Virus-like Particles (VLP) alone.
Consequently, there is still a need for better methods of eliciting, regulating or stimulating an immune response, such as efficient cellular and/or humoral immune responses, against a variety of antigens, such as tumor antigens, viral antigens or other antigens from pathogenic agents by oral or mucosal administration.